2021
Biallelic PI4KA variants cause neurological, intestinal and immunological disease
Salter CG, Cai Y, Lo B, Helman G, Taylor H, McCartney A, Leslie JS, Accogli A, Zara F, Traverso M, Fasham J, Lees JA, Ferla M, Chioza BA, Wenger O, Scott E, Cross HE, Crawford J, Warshawsky I, Keisling M, Agamanolis D, Melver C, Cox H, Elawad M, Marton T, Wakeling M, Holzinger D, Tippelt S, Munteanu M, Valcheva D, Deal C, Van Meerbeke S, Vockley C, Butte MJ, Acar U, van der Knaap MS, Korenke GC, Kotzaeridou U, Balla T, Simons C, Uhlig HH, Crosby AH, De Camilli P, Wolf NI, Baple EL. Biallelic PI4KA variants cause neurological, intestinal and immunological disease. Brain 2021, 144: 3597-3610. PMID: 34415310, PMCID: PMC8719846, DOI: 10.1093/brain/awab313.Peer-Reviewed Original ResearchConceptsOrgan-specific functionsSequence alterationsStructural modelling studyMultiple cell typesCombinatorial biologyHeterotetrameric complexLipid kinasesMolecular partnersFundamental new insightsPhenotypical outcomesFunctional interactionCell typesMembrane phospholipidsTTC7PhosphatidylinositolCritical roleGene alterationsNew insightsHypomyelinating leukodystrophyEfr3Molecular complexesIIIαPI4KAKinaseComplexes
2016
Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline
Hardies K, Cai Y, Jardel C, Jansen AC, Cao M, May P, Djémié T, Le Camus C, Keymolen K, Deconinck T, Bhambhani V, Long C, Sajan SA, Helbig KL, Consortium A, Suls A, Balling R, Helbig I, De Jonghe P, Depienne C, De Camilli P, Weckhuysen S, Afawi Z, Baulac S, Barisic N, Caglayan H, Craiu D, De Kovel C, Lopez R, Guerrini R, Hjalgrim H, Lerche H, Jahn J, Klein K, Koeleman B, Leguern E, Lemke J, Marini C, Muhle H, Rosenow F, Serratosa J, Štěrbová K, Møller R, Palotie A, Striano P, Weber Y, Zara F. Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline. Brain 2016, 139: 2420-2430. PMID: 27435091, PMCID: PMC4995362, DOI: 10.1093/brain/aww180.Peer-Reviewed Original ResearchConceptsProgressive neurological declineEarly-onset refractory seizuresHomozygous missense variantEarly-onset parkinsonismRefractory seizuresNeurological declineOnset parkinsonismNeurodegenerative disease courseAdditional pathogenic variantsMissense variantsDifferent neurological diseasesHomozygous nonsense variantDual phosphatase activityDisease courseRefractory epilepsyTau pathologyClinical spectrumIntractable epilepsySevere epilepsySeizure pathophysiologySynaptic dysregulationLarge cohortSingle patientNeurological diseasesEpilepsy